Isocoumarins, and 3,4-dihydroisocoumarins are known biologically active compounds. Isocoumarins contain the basic ring system: ##STR1## Some substituted isocoumarins are effective as local anesthetics. Other coumarin and isocoumarin derivatives have been reported as having strong hypotensive activity, spasmolytic activity on the sphincter of Oddi and choleretic activity. Still other 4-substituted coumarins for example have been reported as useful as gastric antisecretory agents, with still other coumarin and substituted coumarin compounds being useful as odiferous agents for use in cosmetic preparation, and others as useful intermediates in the preparation of certain known biologically active chromones, as well as certain 7-hydroxycoumarins having known activity as coronary vasodilating activity. It can be seen, therefore, because of the wide range of uses including uses as varied as cosmetic odiferous agents to biologically active compounds for a variety of different pharmacological uses, there is a continuing need for a convenient and efficient synthesis of isocoumarin ring containing compounds, a need which is of contemporary and practical importance.
It is a primary object of the present invention to provide an improved one pot process for preparation of isocoumarin ring containing compounds and 3,5-dihydroisocoumarins from simple benzoic acids.
It is a further object of the present invention to provide isocoumarin ring containing compounds and 3,4-dihydroisocoumarins from simple olefins, dienes, allylic halides, vinyl halides, vinyl esters, and unsaturated cyclopropanes and cyclobutanes by reacting an arene with an electrophilic thallium salt to provide an aryl thallium intermediate compound which is in turn reacted with the olefins, dienes, allylic halides, vinyl halides, vinyl esters, unsaturated cyclopropane or cyclobutane to provide an isocoumarin or a 3,4-dihydroisocoumarin.
It is an additional object of the present invention to avoid the disadvantages of the prior art processes involving complex multi-stage, and step, reactions to prepare isocoumarins from simple benzoic acids.
A still further objective of the present invention is to provide a practical single pot synthesis of isocoumarins and 3,4-dihydroisocoumarins in high yields suitable for commercial use.
The method and manner of accomplishing each of the above objectives as well as others will become apparent from the detailed description which follows.